How the physiological state of an animal can influence social auditory cue recognition and learning at a molecular level represents a gap in knowledge of how our brains favor social information. The physiological state of an animal not only alters the behavioral response and later recognition of conspecific vocalizations, but also modulates auditory cortex plasticity and enhances behavioral learning. Research indicates that hormones, such as estrogen (E), are capable of facilitating social interactions and enhancing auditory social cue learning and memory formation. Our central hypothesis is that an animal's ability to process and remember behaviorally relevant sounds is dependent on its hormonal state, which in turn enacts molecular and behavioral changes detectable at the time of memory encoding and enhances future recognition of the same sounds. We investigate this in a maternal model of vocalization sound learning in mice by controlling a major maternal hormone: E. We will determine what plasticity and memory associated molecular changes are induced in auditory cortical neurons by E-dependent mechanisms and auditory experience with the vocalizations. The proposed research is significant because it will investigate for the first time whether critical molecular signaling pathways for establishing (Aim 1) and maintaining (Aim 2) memories are modulated by E in the mammalian auditory cortex during experience-dependent, communication sound learning. Our long-term goal is to elucidate the neuromodulatory facilitation of social auditory learning. Exposing E's role in social auditory learning will enhance the understanding of our social brain, and identify new therapeutic targets to improve social auditory attention and learning in adults. In line with the mission of NIH, the therapeutic targeting of downstream effectors of E has the potential to improve social auditory attention and language learning in patient populations.